Study of EN-374 Gene Therapy in Participants With X-Linked Chronic Granulomatous Disease

Ensoma

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

X-Linked Chronic Granulomatous Disease

Treatments

Genetic: EN-374

Study type

Interventional

Funder types

Industry

Identifiers

NCT06876363

EN-374-101

Details and patient eligibility

About

The goal of this clinical trial is to evaluate the safety and potential efficacy of the EN-374 treatment regimen and identify a dose level for further evaluation in participants with x-linked chronic granulomatous disease.

The main questions it aims to answer are:

safety of the EN-374 treatment regimen
effect of the EN-374 treatment regimen on the production of functional neutrophils with NADPH oxidase activity

Full description

Chronic granulomatous disease (CGD) is a rare primary immune deficiency disorder characterized by recurrent bacterial or fungal infections starting in infancy. The x-linked form of CGD (X-CGD) is caused by mutations in the CYBB gene.

EN-374 is a helper-dependent adenoviral (HDAd)-based gene therapy in development for the treatment of X-CGD using an in vivo approach, which is administered by IV infusion, to genetically modify hematopoietic stem cells (HSCs) to express a wild-type CYBB gene. The EN-374 treatment regimen includes HSC mobilization, immune prophylaxis, EN-374 administration, and enrichment of genetically modified HSCs.

Adult participants with X-CGD will be enrolled into the dose-escalation part of the study. Following completion of the adult cohorts, then pediatric participants will be enrolled into the dose-expansion part of the study in decreasing age cohorts from ≥ 12 and < 18 years of age, to ≥ 2 and < 12 years of age, and finally to ≥ 3 months and < 2 years of age.

Enrollment

15 estimated patients

Sex

Male

Ages

3+ months old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male
≥ 18 years of age during dose escalation, then ≥ 3 months of age during dose expansion
Diagnosis of X-CGD with DHR+ cells ≤ 5% and a pathogenic mutation in the CYBB gene
History of at least 1 severe infection requiring medical intervention or chronic inflammatory disorder
Does not have a suitable, available, and willing human leukocyte antigens (HLA)-matched (10/10) related donor
Non-sterile male participants who are or may become sexually active with female partners of childbearing potential are required to use highly effective contraception
Informed consent, with informed assent from capable participants
Adequate organ function

Exclusion criteria

Active bacteremia or fungemia
History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
History or clinical evidence of any medical or social issues likely to put the participant at additional risk or to interfere with study conduct
History of HSCT or granulocyte transfusions
Known hypersensitivity to elements in the treatment regimen
Undergone investigational gene therapy
Treated with another investigational drug product within 30 days before screening
Unable to comply with the visits and requirements of the protocol as determined by the Investigator